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Journal of Nutritional Science and... 2023Vascular endothelial cells produce vasoactive substances, such as nitric oxide (NO), to regulate vascular relaxation and contraction. Docosahexaenoic acid (DHA) and...
Vascular endothelial cells produce vasoactive substances, such as nitric oxide (NO), to regulate vascular relaxation and contraction. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) enhance NO production in endothelial cells, and sesamin, a sesame lignan contained in sesame seeds, also promotes NO production. This study examined DHA, EPA, and sesamin's combined effects since it was expected that combining them would further enhance NO production in endothelial cells. Using a human umbilical vein endothelial cell (HUVEC), the NO amount secreted in the culture supernatant was analyzed. Sesamin metabolite (SC1) was used in the experiments because it is a major metabolite in human blood after sesamin absorption. When cells were treated with DHA or EPA alone, they increased NO production in a concentration-dependent manner, whereas no change in NO production was observed for SC1. NO production increased when DHA and EPA were treated in combination with SC1, although the low DHA and EPA concentrations showed no difference in NO production. In the concentrations in which the combined effect was observed, SC1 activated eNOS via calcium signaling, whereas DHA and EPA activated eNOS via alterations in the membrane lipid environment. The combined effect of the two pathways was considered to have enhanced the eNOS activity. These results suggested that combining DHA, EPA, and sesamin might improve vascular endothelial function.
Topics: Humans; Eicosapentaenoic Acid; Docosahexaenoic Acids; Sesamum; Lignans; Human Umbilical Vein Endothelial Cells
PubMed: 37940577
DOI: 10.3177/jnsv.69.370 -
Prostaglandins, Leukotrienes, and... Jul 2022The omega-3 fatty acids (n3-FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) rapidly incorporate into cell membranes where they modulate signal... (Review)
Review
The omega-3 fatty acids (n3-FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) rapidly incorporate into cell membranes where they modulate signal transduction pathways, lipid raft formation, and cholesterol distribution. Membrane n3-FAs also form specialized pro-resolving mediators and other intracellular oxylipins that modulate inflammatory pathways, including T-cell differentiation and gene expression. Cardiovascular (CV) trials have shown that EPA, administered as icosapent ethyl (IPE), reduces composite CV events, along with plaque volume, in statin-treated, high-risk patients. Mixed EPA/DHA regimens have not shown these benefits, perhaps as the result of differences in formulation, dosage, or potential counter-regulatory actions of DHA. Indeed, EPA and DHA have distinct, tissue-specific effects on membrane structural organization and cell function. This review summarizes: (1) results of clinical outcome and imaging trials using n3-FA formulations; (2) membrane interactions of n3-FAs; (3) effects of n3-FAs on membrane oxidative stress and cholesterol crystalline domain formation during hyperglycemia; (4) n3-FA effects on endothelial function; (5) role of n3-FA-generated metabolites in inflammation; and (6) ongoing and future clinical investigations exploring treatment targets for n3-FAs, including COVID-19.
Topics: Cardiovascular Diseases; Cholesterol; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Humans; COVID-19 Drug Treatment
PubMed: 35690002
DOI: 10.1016/j.plefa.2022.102450 -
Neuromolecular Medicine Mar 2021The abundance of docosahexaenoic acid (DHA) in phospholipids in the brain and retina has generated interest to search for its role in mediating neurological functions.... (Comparative Study)
Comparative Study
The abundance of docosahexaenoic acid (DHA) in phospholipids in the brain and retina has generated interest to search for its role in mediating neurological functions. Besides the source of many oxylipins with pro-resolving properties, DHA also undergoes peroxidation, producing 4-hydroxyhexenal (4-HHE), although its function remains elusive. Despite wide dietary consumption, whether supplementation of DHA may alter the peroxidation products and their relationship to phospholipid species in brain and other body organs have not been explored sufficiently. In this study, adult mice were administered a control or DHA-enriched diet for 3 weeks, and phospholipid species and peroxidation products were examined in brain, heart, and plasma. Results demonstrated that this dietary regimen increased (n-3) and decreased (n-6) species to different extent in all major phospholipid classes (PC, dPE, PE-pl, PI and PS) examined. Besides changes in phospholipid species, DHA-enriched diet also showed substantial increases in 4-HHE in brain, heart, and plasma. Among different brain regions, the hippocampus responded to the DHA-enriched diet showing significant increase in 4-HHE. Considering the pro- and anti-inflammatory pathways mediated by the (n-6) and (n-3) polyunsaturated fatty acids, unveiling the ability for DHA-enriched diet to alter phospholipid species and lipid peroxidation products in the brain and in different body organs may be an important step forward towards understanding the mechanism(s) for this (n-3) fatty acid on health and diseases.
Topics: Aldehydes; Animals; Brain; Chromatography, Liquid; Dietary Supplements; Docosahexaenoic Acids; Heart; Lipid Peroxidation; Male; Mice; Mice, Inbred C57BL; Myocardium; Organ Specificity; Oxidation-Reduction; Phospholipids; Plasma; Random Allocation; Tandem Mass Spectrometry
PubMed: 32926329
DOI: 10.1007/s12017-020-08616-0 -
Biomolecules Apr 2023The oral route is considered the most convenient route of drug administration for both systemic and local delivery. Besides stability and transportation, another unmet...
The oral route is considered the most convenient route of drug administration for both systemic and local delivery. Besides stability and transportation, another unmet but important issue regarding oral medication is retention duration within the specific region of the gastrointestinal (GI) tract. We hypothesize that an oral vehicle that can adhere and maintain retention within the stomach for a longer duration can be more effective to treat stomach-related diseases. Therefore, in this project, we developed a carrier that is highly specific to the stomach and maintains its retention for a longer duration. We developed a vehicle composed of β-lucan nd ocosahexaenoic cid () to observe its affinity and specificity to the stomach. GADA forms a spherical-shaped particle with negative zeta potential values that vary based on the feed ratio of docosahexaenoic acid. Docosahexaenoic acid is an omega-3 fatty acid that has transporters and receptors throughout the GI tract, such as CD36, plasma membrane-associated fatty acid-binding protein (FABP (pm)), and a family of fatty acid transport proteins (FATP1-6). The in vitro studies and characterization data showed that GADA has the capability to carry a payload of hydrophobic molecules and specifically deliver the payload to the GI tract, exert its therapeutic effects, and help to maintain stability for more than 12 h in the gastric and intestinal fluid. The particle size and surface plasmon resonance (SPR) data showed that GADA has a strong binding affinity with mucin in the presence of simulated gastric fluids. We observed a comparatively higher drug release of lidocaine in gastric juice than that in intestinal fluids, demonstrating the influence of the pH values of the media on drug-release kinetics. In vivo and ex vivo imaging of mice demonstrated that GADA maintains its retention within the stomach for at least 4 hr. This stomach-specific oral vehicle holds strong promise to translate various injectable therapeutic drugs to oral form upon further optimizations.
Topics: Mice; Animals; Fatty Acids; beta-Glucans; Docosahexaenoic Acids; Drug Delivery Systems; Gastrointestinal Tract; Drug Carriers
PubMed: 37238639
DOI: 10.3390/biom13050768 -
Nutrients Jan 2022The retina requires docosahexaenoic acid (DHA) for optimal function. Alpha-linolenic acid (ALA) and DHA are dietary sources of retinal DHA. This research investigated...
The retina requires docosahexaenoic acid (DHA) for optimal function. Alpha-linolenic acid (ALA) and DHA are dietary sources of retinal DHA. This research investigated optimizing retinal DHA using dietary ALA. Previous research identified 19% DHA in retinal phospholipids was associated with optimal retinal function in guinea pigs. Pregnant guinea pigs were fed dietary ALA from 2.8% to 17.3% of diet fatty acids, at a constant level of linoleic acid (LA) of 18% for the last one third of gestation and retinal DHA levels were assessed in 3-week-old offspring maintained on the same diets as their mothers. Retinal DHA increased in a linear fashion with the maximum on the diet with LA:ALA of 1:1. Feeding diets with LA:ALA of 1:1 during pregnancy and assessing retinal DHA in 3-week-old offspring was associated with optimized retinal DHA levels. We speculate that the current intakes of ALA in human diets, especially in relation to LA intakes, are inadequate to support high DHA levels in the retina.
Topics: Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Diet; Dietary Fats; Docosahexaenoic Acids; Female; Guinea Pigs; Linoleic Acid; Maternal Nutritional Physiological Phenomena; Phospholipids; Pregnancy; Retina; alpha-Linolenic Acid
PubMed: 35057481
DOI: 10.3390/nu14020301 -
International Journal of Molecular... Mar 2022Although the human lifespan has increased in the past century owing to advances in medicine and lifestyle, the human healthspan has not kept up the same pace, especially... (Review)
Review
Although the human lifespan has increased in the past century owing to advances in medicine and lifestyle, the human healthspan has not kept up the same pace, especially in brain aging. Consequently, the role of preventive health interventions has become a crucial strategy, in particular, the identification of nutritional compounds that could alleviate the deleterious effects of aging. Among nutrients to cope with aging in special cognitive decline, the long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have emerged as very promising ones. Due to their neuroinflammatory resolving effects, an increased status of DHA and EPA in the elderly has been linked to better cognitive function and a lower risk of dementia. However, the results from clinical studies do not show consistent evidence and intake recommendations for old adults are lacking. Recently, supplementation with structured forms of EPA and DHA, which can be derived natural forms or targeted structures, have proven enhanced bioavailability and powerful benefits. This review summarizes present and future perspectives of new structures of ω-3 LCPUFAs and the role of "omic" technologies combined with the use of high-throughput in vivo models to shed light on the relationships and underlying mechanisms between ω-3 LCPUFAs and healthy aging.
Topics: Adult; Aged; Aging; Cognition; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Humans
PubMed: 35408832
DOI: 10.3390/ijms23073472 -
The Journal of Biological Chemistry Mar 2022Pulmonary surfactant is a lipoprotein complex essential for lung function, and insufficiency or altered surfactant composition is associated with major lung diseases,...
Pulmonary surfactant is a lipoprotein complex essential for lung function, and insufficiency or altered surfactant composition is associated with major lung diseases, such as acute respiratory distress syndromes, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. Pulmonary surfactant is primarily composed of phosphatidylcholine (PC) in complex with specialized surfactant proteins and secreted by alveolar type 2 (AT2) cells. Surfactant homeostasis on the alveolar surface is balanced by the rates of synthesis and secretion with reuptake and recycling by AT2 cells, with some degradation by pulmonary macrophages and loss up the bronchial tree. However, whether phospholipid (PL) transporters exist in AT2 cells to mediate reuptake of surfactant PL remains to be identified. Here, we demonstrate that major facilitator superfamily domain containing 2a (Mfsd2a), a sodium-dependent lysophosphatidylcholine (LPC) transporter, is expressed at the apical surface of AT2 cells. A mouse model with inducible AT2 cell-specific deficiency of Mfsd2a exhibited AT2 cell hypertrophy with reduced total surfactant PL levels because of reductions in the most abundant surfactants, PC containing dipalmitic acid, and PC species containing the omega-3 fatty acid docosahexaenoic acid. These changes in surfactant levels and composition were mirrored by similar changes in the AT2 cell lipidome. Mechanistically, direct tracheal instillation of fluorescent LPC and PC probes indicated that Mfsd2a mediates the uptake of LPC generated by pulmonary phospholipase activity in the alveolar space. These studies reveal that Mfsd2a-mediated LPC uptake is quantitatively important in maintaining surfactant homeostasis and identify this lipid transporter as a physiological component of surfactant recycling.
Topics: Animals; Docosahexaenoic Acids; Homeostasis; Lung; Lysophosphatidylcholines; Membrane Transport Proteins; Mice; Phosphatidylcholines; Phospholipids; Pulmonary Surfactants; Symporters
PubMed: 35150739
DOI: 10.1016/j.jbc.2022.101709 -
Nutrients Nov 2022An observational comparative study was designed to assess the fatty acids profile in erythrocyte membrane phospholipids of 30 preterm neonates (<32 weeks gestation) at...
An observational comparative study was designed to assess the fatty acids profile in erythrocyte membrane phospholipids of 30 preterm neonates (<32 weeks gestation) at birth and after 1 month of life versus a convenience sample of 10 infants born at term. The panel of fatty acids included the families and components of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and n-6 and n-3 polyunsaturated fatty acids (PUFAs) as well as enzyme activity indexes and fatty acids ratios. At birth, the comparison of fatty acid families between preterm and term neonates showed a significantly higher content of SFAs and n-6 PUFAs, and a significantly lower content of MUFAs and n-3 PUFAs in the preterm group. After 30 days of life, significantly higher levels of n-6 PUFAs and significantly lower levels of n-3 PUFAs among preterm neonates persisted. At 30 days of birth, n-6 PUFA/n-3 PUFA and arachidonic acid (ARA) ARA/DHA remained significantly elevated, and DHA sufficiency index significantly decreased in the preterm group. The pattern of n-3 PUFA deficiency at birth and sustained for the first month of life would support the need of milk banking fortified with DHA and the use of DHA supplementation in breastfeeding mothers.
Topics: Infant; Humans; Infant, Newborn; Docosahexaenoic Acids; Infant, Premature; Erythrocyte Membrane; Milk, Human; Fatty Acids, Omega-6; Fatty Acids, Omega-3; Fatty Acids
PubMed: 36500985
DOI: 10.3390/nu14234956 -
Journal of Nutritional Science 2023This study aimed to determine the association of serum docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels with dietary intakes and supplement use during... (Observational Study)
Observational Study
This study aimed to determine the association of serum docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels with dietary intakes and supplement use during pregnancy. This prospective observational study was conducted at a university hospital in Tokyo, Japan. Participants in their second and third trimesters were given a self-administered questionnaire assessing the frequency of DHA and EPA supplement use in the past month and a brief-type self-administered diet history questionnaire. Non-fasting serum DHA and EPA levels were analysed using gas chromatography. Differences in biomarkers by frequency of supplement use were determined using multiple comparison analyses, and Spearman's correlation coefficient was used to determine biomarkers and DHA and EPA intakes by food group. Of the 116 participants, 11 (9⋅5 %) in the second trimester and 18 (15⋅5 %) in the third trimester regularly used supplements (≥5 times per week). Regular users had higher serum DHA and EPA levels than never users in the second and third trimesters. Dietary DHA and EPA intake from fish and shellfish was positively correlated with serum DHA and EPA in the second and third trimesters. Supplement use ≥5 times per week and fish and shellfish intake were associated with high serum DHA and EPA levels.
Topics: Animals; Female; Humans; Pregnancy; Biomarkers; Dietary Supplements; Docosahexaenoic Acids; Eating; Eicosapentaenoic Acid; Prospective Studies
PubMed: 38155803
DOI: 10.1017/jns.2023.105 -
Journal of Oleo Science Oct 2021Dietary fish oil containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been reported to affect the diversity and composition of gut microbiota and...
Dietary fish oil containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been reported to affect the diversity and composition of gut microbiota and bacterial metabolites. However, few reports have focused on the effects of EPA and DHA on gut microbiota diversity and bacterial metabolites. This study evaluated the effects of dietary EPA-ethyl ester (EE) and DHA-EE on steroid metabolism, gut microbiota, and bacterial metabolites in Wistar rats. Male rats were fed the experimental diets containing 5% (w/w) soybean oil-EE (SOY diet), EPA-EE (EPA diet), and DHA-EE (DHA diet) for four weeks. The lipid contents in the serum and liver, mRNA expression levels in the liver, and the diversity, composition, and metabolites of the gut microbiota were evaluated. The EPA and DHA diets decreased serum and liver cholesterol contents compared to the SOY diet. In addition, there were no significant changes in gene expression levels related to steroid metabolism in the liver between the EPA and DHA groups. Rats fed the DHA diet had lower microbiota diversity indices, such as Simpson and Shannon indices, than rats fed the SOY and EPA diets. In addition, rats fed EPA and DHA had significant differences in the relative abundance of microbiota at the genus level, such as Phascolarctobacterium, Turicibacter, and [Eubacterium]. Therefore, it was concluded that EPA and DHA have different effects on the diversity and composition of gut microbiota under the experimental conditions employed herein.
Topics: Animals; Bacteria; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Esters; Eubacterium; Firmicutes; Gastrointestinal Microbiome; Lipid Metabolism; Liver; Male; Microbiota; Rats, Wistar; Veillonellaceae; Rats
PubMed: 34497184
DOI: 10.5650/jos.ess21189